Radioactive isotope generator of short-lived nuclides

ABSTRACT

A radioactive isotope generator for conducting parent-daughter radio-nuclide separations and containing a relatively small amount of radioactivity, the generator comprising a container or column having a parent nuclide disposed therein, the parent nuclide being separated from the remainder of the column by a filter material. As a specific embodiment, the generator comprises a column having two chambers separated by a filter material, the parent activity being adsorbed on an adsorbent such as alumina and being disposed in one of the chambers as a suspension. The open end of the column proximate the empty chamber is sealed by a puncturable stopper. By evacuating the empty chamber by means of a syringe inserted through the puncturable stopper, for example, the solution containing the daughter nuclide will pass through the filter and into the empty chamber, from which it is available for use.

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nited 1. 3,740,558 Kato et al. June 19, 1973 [5 RADIOACTIVE ISOTOPE GENERATOR OF Primary Examiner-Archie R. Borchelt SHORT-LIVED NUCLIDES Assistant Examiner-Davis L. Willis [7 5] Inventors: Sadatake Kato, Tokyo; Attorney-ROM" Nblack Kunio Kurata, Matsudo,

both of Japan ABSTRACT A radioactive isotope generator for conducting parentdaughter radio-nuclide separations and containing a relativelysmall amount of radioactivity, the generator [73] Assignee: Dainabot Radioisotope Laboratories,

LTD, Tokyo, Japan [22] Filed: 17, 1971 comprising a container or column having a parent nuclide disposed therein, the parent nuclide being sepa- 1 pp 116,055 rated from the remainder of the column by a filter material. As a specific embodiment, the generator com- 521 U.S. c1. 250/106 T, 250/108 R prises a Column having two Chambers Separated y a 51 1m. (:1. G2lh 5/00 filter material, the parent activity being adsorbed on an 58 Field of Search 250/106 T, 106 s, adsorbent Such as alumina and being disposed in one of 250/106 R 103 141/27 the chambers as a suspension. The open end of the col- I umn proximate the empty chamber is sealed by a punc- [56] References Cited turable stopper. By evacuating the empty chamber by UNITED STATES PATENTS means of a syringe inserted through the puncturable stopper, for example, the solution containing the daughter nuclide will pass through the filter and into 3:576:998 5 1971 Deotsch 250/106 T the empty chambe fmm whch avalab'e for 5 Claims, 5 Drawing Figures EMS-52553 1:2 I; REM +32% Patented June 19, 1973 O a l H 6 mf 1 2 M a aw w H H n u "T n u I U n r i If I: V C. 0 (Hill. I EU. 3 I f. l iflwul a n l Ill: |l|.l 0 5 RADIOACTIVE ISOTOPE GENERATOR OF SHORT-LIVED NUCLIDES BACKGROUND OF THE INVENTION To perform a diagnosis of a patient using radiopharmaceuticals without undue radiation dosage, shortlived nuclides are particularly attractive. However, the short-lived radiopharmaceuticals lose much of their radioactivity during their transportation from the manufacturer to hospitals and their storage at the hospitals. To use them effectively, it is necessary to be near a source of production of short-lived nuclides, or to use what is called a nuclide generator. This device makes short-lived nuclides available at long distances from the source of production and consists of a longer-lived parent nuclide that produces a short-lived daughter nuclide as it decays. Usually the daughter nuclide is separated by chemical means as it is needed and the parent is left to generate a fresh daughter.

A generator is based on the principle that a daughter nuclide can be separated readily and repeatedly from its longer-lived parent nuclide. Differences in chemical behavior are used to achieve the separation. The general relationship between parent and daughter radioactivity can be derived from the interaction of the decay constants of the two radionuclides. After the daughter nuclide has been removed from the parent, the daughter activity increases progressively as the parent decays until they reach a state of transient equilibrium, at which point the ratio of the two activities remains constant and both appear to decay with the half-life of the parent. A typical commercially available generator for medical use of 99m technetium (99m Tc) consists ofa small glass column containing aluminum oxide on which the parent activity 99 molybdenum (99 M) is firmly adsorbed The alumina is retained in the tube by a porous glass disk. The daughter activity is eluted from the generator by pouring the proper reagents on the top of the column and collecting the eluate from the bottom. In most of the cases an outer housing made of lead protects the operator from the radiation.

However, this type of generator offers several disadvantages to hospital personnel:

1. Elution efficiency is sometimes unsatisfactorily low and inconstant.

2. They are supplied as much as 50 to 200 mCi of 99 Mo per, column commercially, which require heavy lead shields for radiation protection, and give more opportunity of undue radiation exposure to hospital personnel.

3. Because of the high radioactivity in a column, the generator is expensive and uneconomical for the hospitals which have small numbers of patients daily.

To solve these problems, eluted daughter nuclide solution (i.e., 99m Tc) are now distributed to hospitals which are at convenient locations from manufacturers. However, its very short shelf-life still offers inconvenience to hospital personnel.

SUMMARY OF THE INVENTION The nuclide generator of the present invention con tains to millicuries (mCi) of 99 Mo; which is uniformly adsorbed on alumina, or other appropriate adsorbents. The adsorbents can be supplied in sterile state either as suspension in appropriate solution or as a dry powder. In any one of the illustrated generators, the parent nuclide is uniformly adsorbed on the adsorbent and the solution can be mixed well and long enough with the adsorbent to give constant and high extraction efficiency of the daughter nuclide. The extraction procedures are simple and easy, and because of the lower contents of radioactivity per bottle, decrease the price and the possibility of undue radiation. The shelf-life of the product depends upon the half-life of the parent nuclide, not upon the shorter lived daughter nuclides half-life.

DRAWINGS The invention will be better understood with reference to the following drawings in which:

FIG. 1 is a side elevational view in cross-section of a nuclide generator having a suspension of the adsorbent and parent nuclide therein.

FIG. 2 is a side elevational view in cross-section of a nuclide generator having dry adsorbent therein.

FIG. 3 is a side elevational view in cross-section of another embodiment of a nuclide generator having a suspension of the adsorbent and parent nuclide therein.

FIG. 4 is a side elevational view of an embodiment of the invention in which the adsorbent is contained within a filter pack.

FIG. 5 is a side elevational view in cross-section of a further embodiment of the invention employing dry adsorbent.

DETAILED DESCRIPTION The alumina powder on which is adsorbed 99 molybdenum (99 M0) is prepared as follows. To l0 ml. of nitric acid solution of a pH of 2.4 and containing 10 millicuries (mCi) of 99 Mo as ammonium molybdate, 0.5 grams of well-washed alumina powder is added and mixed well for about one minute. After filtration and washing, the alumina powder is dried and dispensed into the generators as described hereinafter.

In this procedure the alumina can be replaced with ZrO MgO-SiO gel or SiO XI-I O gel. When alumina is used as the adsorbent for 99 M0, the most optimal pH of the 99 Mo solution for the best adsorption is 2.4, although adsorption can take place between a pH of 1.5 4.5.

Extraction of the daughter nuclide solution utilizing the various embodiments of the invention is conducted as follows. Illustrated in FIG. 1 is a nuclide generator 10 comprising a tubular column 11 having open ends. The openings in the ends of the column 10 end are sealed by puncturable stoppers 12, 13 and the column 11 is divided into two chambers 14, 15 by a filter 16. Disposed in one chamber 14 is a suspension 17 of the adsorbent and parent nuclide. If the daughter nuclide is to be used for medical purposes, the suspension can be prepared with saline. To extract the daughter nuclide solution, the empty chamber 15 is evacuated by puncturing the stopper 13 with the needle of a syringe and withdrawing the air. The syringe is then withdrawn and the generator 10 turned upside-down whereby the solution containing the daughter nuclide will pass through the filter 16 into the empty chamber 15. The solution can then be withdrawn for use through the puncturable stopper 13. In the embodiment illustrated in FIG. 2, dried adsorbent 18 is disposed in the chamber 14. To utilize the generator 10, saline solution is injected into the chamber 14 containing the dried adsorbent 18 through the puncturable stopper 12. The generator 10 is then shaken vigorously and the daughter nuclide solution is extracted in the same manner as de:

scribed for the embodiment illustrated in FIG. 1.

F IG. 3 illustrates a further embodiment of the nuclide generator comprising a container 21 having an open end. The open end is sealed by a puncturable stopper 22 from which depends a tubular element 23, the end of the tubular element 23 away from the stopper 22 being sealed with a filter 24. A suspension of the adsorbent in saline solution is disposed in the container 21, the tubular element 23 being immersed therein. The daughter nuclide solution passes through the filter 24 and into the tubular element 23 from which it can be withdrawn by means of a syringe inserted through the puncturable stopper 22.

FIG. 4 illustrates a further embodiment of a generator comprising a container 31 having an open end sealed by a puncturable stopper 32. Disposed within the container 31 is dried adsorbent contained in a filter pack 33. Saline solution is added to the container 31 with a syringe inserted through the puncturable stopper 32. The generator 30 is then shaken vigorously and the daughter nuclide solution withdrawn through the puncturable stopper 32.

FIG. 5 illustrates a nuclide generator comprising a tubular element 41 having an open end. Inserted into the tubular element 41 is a barrel 42 of a syringe 43 having a plunger and piston 44 fitted within the barrel 42 to form a first chamber 45 containing saline solution. The open end 46 of the barrel 42 and chamber 45 is sealed by a rubber stopper 47 containing a filter 48, the stopper 47 fitting tightly within the tubular element 41 to thereby act as a piston. Dried adsorbent 49 is disposed within the chamber 50 formed by the tubular element 41 and stopper 47. To utilize the generator, the plunger 44 of the syringe 43 is depressed to transfer the saline solution from the first chamber 45 through the filter 48 and into the second chamber 50 where it contacts the dried adsorbent 49 and parent nuclide. The generator is shaken vigorously and the daughter nuclide solution is then withdrawn into the chamber 45 of 40 the syringe 43 through the filter by depressing the barrel 42 of the syringe 43 into the tubular element 41. The syringe 43 containing the daughter nuclide solution is then removed from the tubular element 41.

What is claimed is:

1. A radioactive isotope generator comprising a container having an open end and containing a radioactive parent nuclide from which can be extracted a daughter nuclide solution to be utilized for diagnosing and treatment of medical conditions, the open end of the container being sealed by a puncturable stopper, a suspension of radioactive parent nuclide material disposed in said container, and a tubular element depending from said puncturable stopper and at least partially immersed in the suspension of parent nuclide, the end of the tubular element away from the stopper being sealed with a filter whereby the daughter nuclide solution can pass through the filter and into the tubular element from which it can be withdrawn through the puncturable stopper.

2. The radioactive isotope generator of claim 1 wherein the suspension comprises 5 to 20 millicuries of 99 molybdenum suspended in saline solution.

3. A radioactive isotope generator comprising a tubular element having an open end, walls and a closed end and a syringe slidable within said tubular element, said syringe comprising a barrel portion having an opening and a plunger and piston reciprocally movable within the barrel of the syringe, the piston and barrel defining a first chamber, the opening in the barrel portion opposite the piston being sealed by a stopper containing a filter, the stopper being slidably engageable with the walls of the tubular element and defining a second chamber, the opening in the barrel portion of said first chamber being in communication, through said filter contained in the stopper, with said second chamber, eluting solution disposed in said first chamber and transferable through said filter into said second chamber when the plunger and piston is depressed, and a sterile, radioactive parent nuclide material disposed in said second chamber.

4. The radioactive isotope generator of claim 3 wherein the parent nuclide material is 99 molybdenum and the eluting solution is saline solution.

5. The radioactive isotope generator of claim 4 wherein the parent nuclide material contains from 5 to 20 millicuries of radioactivity. 

1. A radioactive isotope generator comprising a container having an open end and containing a radioactive parent nuclide from which can be extracted a daughter nuclide solution to be utilized for diagnosing and treatment of medical conditions, the open end of the container being sealed by a puncturable stopper, a suspension of radioactive parent nuclide material disposed in said container, and a tubular element depending from said puncturable stopper and at least partially immersed in the suspension of parent nuclide, the end of the tubular element away from the stopper being sealed with a filter whereby the daughter nuclide solution can pass through the filter and into the tubular element from which it can be withdrawn through the puncturable stopper.
 2. The radioactive isotope generator of claim 1 wherein the suspension comprises 5 to 20 millicuries of 99 molybdenum suspended in saline solution.
 3. A radioactive isotope generator comprising a tubular element having an open end, walls and a closed end and a syringe slidable within said tubular element, said syringe comprising a barrel portion having an opening and a plunger and piston reciprocally movable within the barrel of the syringe, the piston and barrel defining a first chamber, the opening in the barrel portion opposite the piston being sealed by a stopper containing a filter, The stopper being slidably engageable with the walls of the tubular element and defining a second chamber, the opening in the barrel portion of said first chamber being in communication, through said filter contained in the stopper, with said second chamber, eluting solution disposed in said first chamber and transferable through said filter into said second chamber when the plunger and piston is depressed, and a sterile, radioactive parent nuclide material disposed in said second chamber.
 4. The radioactive isotope generator of claim 3 wherein the parent nuclide material is 99 molybdenum and the eluting solution is saline solution.
 5. The radioactive isotope generator of claim 4 wherein the parent nuclide material contains from 5 to 20 millicuries of radioactivity. 